California Poppy Traditionally used for several disorders “Reactive, agitated and masked depressions, melancholy, neurasthenia, neuropathy, organ neurosis, vegetative-dystonic disturbances, imbalances, constitutional lability of the nervous system”, as well as a sleep-inducer and sedative tea. ⦁ Affinity for the benzodiazepine receptors and alkaloids increase the binding of GABA to GABA receptors ⦁ Binding to 5-HT1A and 5-HT7 receptors Relative safety is evidenced by traditional use of the plant, which can be found in the European market for more than 30 years without any safety concern. The California poppy is known in folk medicine for its sedative, anxiolytic, and antinociceptive effects. These effects have been traditionally assigned to protopine and allocryptopine. Both alkaloids act as weak stimulators of the binding of GABAA receptor agonists in the rat brain, as anti-inflammatory agents and as acetylcholinesterase inhibitors. Another aporphine alkaloid isolated from this plant, namely, N-methyllaurotetanine (NMT), was reported to act as antagonist at the serotonin 5 receptor (EC50 = 155 nM, nM). Protopine and allocryptopine were also found to block human serotonin and noradrenaline transporters (hSERT and NERT) and possess antidepressant-like effects on animal models. However, it is not clear whether typical pharmacy preparations (i.e., 300 mg of dry plant material per capsule) contain sufficient quantities of these alkaloids required to induce desired biological effects. Even though the presence of NMT in this plant has been clearly established, its content in the aerial parts of this perennial herb is currently unknown. [Take home point]: It is evident from HPLC analysis that protopine and α-allocryptopine levels in the aerial parts of this herb are too low to modulate significantly the chloride-ion flow across the GABAA receptors at traditional doses. You have to go beyond the 300mg doses... in order to achieve important medicinal effects (regarding relatively low alkaloid levels determined in aerial parts of this plant), one would need to increase 1 the dried plant dosage above 1 g Source: https://doi.org/10.1155/2015/617620 The aqueous extract of the plant at 25mg/kg in mice exerted an anxiolytic action, as proved by changes in behavioural parameters; at higher levels, the effect became more sedative. The anxiolytic and sedative effects of E. californica are caused by affinity for GABA receptors, as evidenced by suppression of anxiolytic and sedative effects following pre- treatment with flumazenil. Both aerial parts and roots contain alkaloids, the latter being MUCH richer (1.6-2.7%) 2